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March 15, 2013

Understanding Obesity And How Brown Fat Cells Form

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Enid Burns for redOrbit.com — Your Universe Online

Many of us don't know the difference between brown fat cells and white fat cells. But researchers at Perelman School of Medicine at the University of Pennsylvania, led by Patrick Seale, Ph.D., are looking at brown fat cells to better understand how they develop.

The researchers believe that the brown fat cell makes heat for the body, which has helped mammals cope with the cold. New theories say the warmth generated in brown fat cells might also be able to help those dealing with obesity and diabetes, among other health conditions.

"Brown fat cells are the professional heat-producing cells of the body," said Seale, in a statement from the university. "Because of this they are protective against obesity as well as diabetes." Seale is an assistant professor of Cell and Developmental Biology, and a member of the Institute for Diabetes, Obesity and Metabolism.

Findings of the research are published this week in Cell Metabolism. In addition to Seale and others at the University of Pennsylvania, other contributors to the research include postdoctoral fellow Sona Rajakumari, Ph.D. and Jun Wu from the Dana-Farber Cancer Institute.

During the research, the group found that a protein switch called early B cell factor-2 (Ebf2) determines which developmental path fat precursor cells take. This determines the brown fat cells versus white fat cells.

One of the findings in the research is that the Ebf2 regulates the binding activity of PPAR-gamma, a protein that regulates differentiation of developing cell types. This is the target of anti-diabetic drugs. Ebf2 affects PPAR-gamma cell's ability to determine if precursor cells go down the white or brown fat cell path. The conclusion is that Ebf2 may alter epigenetic proteins at brown fat genes to expose PPAR-gamma binding sites.

"Brown fat cells are thought to counteract obesity by burning off excess energy stored in lipid, but white fat cells store energy," the report says. Brown fat cells contain smaller droplets of lipids and the most mitochondria (containing pigmented cytochromes that bind iron) of any cell type. This is the factor that makes these cells brown. A genome-wide study of PPAR-gamma binding regions conducted by Rajakumari looked at white versus brown fat cells. She found that brown cell-specific binding sites also contain a DNA-recognition site for Ebf2 transcription factors. She also found that Ebf2 is strongly expressed only in brown fat cells. When Ebf2 is overexpressed in precursor white fat cells, they matured into brown fat cells.

EBf2 occurs as the earliest protein in the timeline of the development and differentiation of brown fat cells. "Many times the earlier in the developmental stage that a guiding protein is active, the more powerful it is in driving a certain process of differentiation," notes Seale. "Ebf2 is not really a readily druggable target, but perhaps a protein related to it is."

The research was funded by the Functional Genomics Core of the Penn Diabetes and Endocrinology Research Center, and a Searle Scholars Award. Co-authors include Hee-Woong Lim and K.J. Won from the Department of Genetics.